Recently, there have been a growing number of reports on serious fungal infections in immunocompromised cancer patients undergoing chemotherapies, organ transplant recipients, AIDS patients, etc. Most of the fungal infections are known to be caused by opportunistic pathogens such as Candida spp., Aspergillus spp. and Cryptococcus neoformans. Accordingly, for the future elderly society, development of medical countermeasures against emerging infectious diseases caused by pathogens including resistant bacteria will become an important issue.
The number of antifungal agents available at present is much less than that of antibiotics used for the treatment of bacterial infections. Examples of the antifungal agents developed so far include polyene antifungals such as amphotericin B or azole antifungals such as fluconazole, itraconazole, voriconazole, posaconazole, etc. However, the appearance of azole-resistant fungi has become a problem. Recently, cyclic hexapeptide type echinocandins from natural products (caspofungin, micafungin, and anidulafungin) have been developed as a new class of antifungals, 1,3-β-glucan synthase.
Additionally, benzimidazole compounds have been widely used as therapeutic agents such as parasiticides, antifungals, antiulcer drugs, etc., and thiabendazole, the representative benzimidazole antifungal, is known to have a structure similar to those of benzimidazole compounds. Procodazol, being a benzimidazole derivative, has a broad spectrum in the treatment of parasitic or fungal infections. Formulations containing the compound as an active ingredient, when orally administered, exhibit antifungal effects against infections caused by dermatomycoses such as Paracoccidioidomycosis and Histoplasmosis. Furthermore, benzimidazole compounds containing an aryl group or heteroarylalkanoic acid have been developed as non-steroid anti-inflammatory agents.
The antifungal agents may be classified into fungistatics and fungicides depending on the effects of their actions. Generally, fungicidal agents have a high clinical value due to their rapid and strong actions. Amphotericin B and echinocandins are known to be effective for the treatment of systemic mycoses. However, these fungicidal agents have only a limited use as they can be used in the form of injection only, and thus there is an unmet need for the development of a fungicidal agent for oral administration.